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Structure of the Complex between a Heparan Sulfate Octasaccharide and Mycobacterial Heparin‐Binding Hemagglutinin
Author(s) -
Huang TengYi,
Irene Deli,
Zulueta Medel Manuel L.,
Tai TzuJui,
Lain ShihHan,
Cheng ChengPo,
Tsai PingXi,
Lin ShuYi,
Chen ZhiGeng,
Ku ChiaoChu,
Hsiao ChwanDeng,
Chyan ChiaLin,
Hung ShangCheng
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201612518
Subject(s) - chemistry , mycobacterium tuberculosis , hemagglutinin (influenza) , heparan sulfate , binding site , virulence factor , nuclear magnetic resonance spectroscopy , heparin , plasma protein binding , virulence , mycobacterium tuberculosis complex , biochemistry , biophysics , stereochemistry , biology , tuberculosis , gene , medicine , pathology
Abstract Heparin‐binding hemagglutinin (HBHA) is a 199 amino acid virulence factor at the envelope of Mycobacterium tuberculosis that contributes to latent tuberculosis. The binding of HBHA to respiratory epithelial cells, which leads to extrapulmonary dissemination of the pathogen, is mediated by cell‐surface heparan sulfate (HS). We report the structural characterization of the HBHA/HS complex by NMR spectroscopy. To develop a model for the molecular recognition, the first chemically synthesized uniformly 13 C‐ and 15 N‐labeled HS octasaccharide and a uniformly 13 C‐ and 15 N‐labeled form of HBHA were prepared. Residues 180–195 at the C‐terminal region of HBHA show large chemical shift perturbation upon association with the octasaccharide. Molecular dynamics simulations conforming to the multidimensional NMR data revealed key electrostatic and even hydrophobic interactions between the binding partners that may aid in the development of agents targeting the binding event.